A Study on the Effects of Intranasally Administered Liquid Crystalline Nanoparticles Loaded with Salvianolic Acid B in Vascular Dementia.

Salvianolic acid B (SalB) is a bioactive polyphenol with therapeutic potential for vascular dementia (VD), but poor penetration across the blood-brain barrier (BBB) and low bioavailability restrict its clinical translation. To address these problems, a SalB-loaded liquid crystalline nanoparticle delivery system (SalB-LCN) was constructed and systematically characterized in terms of its physicochemical properties. Meanwhile, an intranasal administration strategy was employed to bypass the BBB, and the therapeutic effects of SalB-LCN on VD were systematically evaluated. The results showed that SalB-LCN possessed favorable morphology and sustained-release properties, enabling stable encapsulation and continuous release of SalB. In vitro experiments demonstrated that SalB-LCN exhibited good biocompatibility and could alleviate oxidative damage in neuronal cells. In a bilateral common carotid artery occlusion-induced rat model of VD, SalB-LCN significantly improved learning and memory abilities, alleviated hippocampal neuronal morphological damage, and exhibited good in vivo biosafety. Further studies showed that SalB-LCN markedly lowered reactive oxygen species levels, suppressed IL-1β and IL-18 production in hippocampal tissues, and reduced cell death as well as lactate dehydrogenase activity. In addition, SalB-LCN also suppressed NLRP3/Caspase-1/GSDMD signaling. In conclusion, intranasal delivery of SalB-LCN improved brain delivery by facilitating transport across the BBB and conferred neuroprotection against VD through modulation of oxidative stress, inflammation, and NLRP3/Caspase-1/GSDMD signaling, highlighting its translational potential as a nanomedicine-based therapeutic strategy.